Formation of an Emulsion in a Fluid Microsystem

ABSTRACT

There is described a method for forming an emulsion ( 1 ) containing at least one dispersed phase ( 3 ) and a continuous phase ( 2 ) in a fluidic microsystem ( 100 ), said method comprising the steps: forming flows ( 4, 5 ) of different liquids which flow towards a dispersion region ( 10 ), and forming the emulsion ( 1 ) from the liquids in the dispersion region ( 10 ), wherein the flows ( 4, 5 ) run through a common channel ( 20 ) to the dispersion region ( 10 ) and the flows ( 4, 5 ) are arranged next to one another relative to a first reference direction, and wherein the emulsion ( 1 ) is produced as the liquids flow through a cross-sectional widening ( 11 ) provided in the dispersion region ( 10 ), at which the cross section of the channel ( 20 ) widens in a second reference direction different from the first reference direction. A fluidic microsystem for forming an emulsion ( 1 ) containing a continuous phase ( 2 ) and at least one dispersed phase ( 3 ) is also described. A fusion of droplets in electric fields is also described.

The invention relates to a method for forming an emulsion in a fluidicmicrosystem, wherein a continuous and at least one dispersed phase ofthe emulsion are produced from at least two different liquids in adispersion region of the microsystem. The invention also relates to afluidic microsystem which has at least one dispersion region for formingthe emulsion. The invention also relates to a method for processing anemulsion in a fluidic microsystem, wherein droplets of a dispersed phaseare fused under the effect of an electric field. The invention alsorelates to a fusion device for fusing dispersed droplets by means ofelectrocoalescence.

It is generally known to use fluidic microsystem technology inparticular for chemical, biochemical, pharmaceutical or medicalanalyses. A fluidic microsystem contains channels or cavities havingtypical cross-sectional dimensions in the sub-mm range, through whichliquids can flow. In the microsystem, the liquids or particles suspendedtherein can undergo physical or chemical treatments or measurements. Oneparticular property of fluidic microsystems is that, due to the smallcross-sectional dimensions, the flows are typically laminar and free ofeddies, so that targeted control of the flows is possible. Onesignificant advantage, particularly for chemical applications(“lab-on-a-chip”), is provided by the low substance consumption whenusing the microsystem technique.

A new branch of fluidic microsystem technology that has been developedis known as digital microfluidics, in which a liquid in the microsystemconsists not of individual phases but rather of a plurality of phases(compartments) which are delimited from one another. Thecompartmentalized liquid forms a dispersion (emulsion) consisting of twoor more liquids which do not mix within the microsystem. The use ofcompartmentalized liquids has the particular advantage that thesubstance consumption can be further reduced since e.g. one specificreaction partner is contained in only a few droplets of a dispersedphase of the emulsion. A further advantage consists in the completeprevention of axial dispersion in the compartmentalized liquid (see e.g.H. Song et al. in “Angew. Chem.”, vol. 792, 2003, page 1145).

Various techniques for forming emulsions in fluidic microsystems areknown, which differ by the mechanism for producing and distributingdroplets of the dispersed phase in a continuous phase. In the so-calledjet technique (see e.g. Y-C. Tan et al. in “LabChip”, vol. 4, 2004,pages 292-298), an initially single-phase liquid, which after formationof the emulsion is to form the dispersed phase, flows at a high speedinto a surrounding fluid which is to form the continuous phase afterformation of the emulsion. During this, a liquid jet which is delimitedfrom the surroundings is produced, which as a result of the so-calledRayleigh instability breaks down into individual droplets after apredefined jet length. Disadvantages of the jet technique are that itcannot readily be implemented in the microsystem during continuousoperation (“on-line”), but rather requires the production of theemulsion outside the microsystem (“off-line”). There are alsodisadvantages since the rapidly flowing liquid jet results in a highsubstance consumption and low controllability of the emulsion formation.In the shear technique (see T. Thorsen et al. in “Phys. Review Letters”,vol. 86, 2001, pages 4163-4166), the emulsion is formed at a T-junctionof two channels. At the T-junction, the phase to be dispersed is pressedlaterally into the continuous phase flowing in a straight line, whereinthe emulsion is formed by a regular shear process at the T-junction. Theshear technique has disadvantages since the monodispersity of thedroplets produced and the possibility of producing emulsions containinga small volume of the continuous phase are limited.

In fluidic Microsystems, it is not only the production of dispersionsthat is of interest, but also the targeted fusion of dispersion dropletsin order for example to trigger chemical reactions of reaction partnersin adjacent droplets. It is known to fuse dispersion droplets under theeffect of an electric field (so-called electrocoalescence). By way ofexample, electrocoalescence using electrodes in a fluidic microsystem isdescribed by J. and G. Kralj et al. in “Lab Chip”, vol. 5, 2005, page531, and in WO 2006/027757. The electrodes are arranged a certaindistance apart in the longitudinal direction of a channel of themicrosystem. When dispersed droplets are located in the gap between theelectrodes, the droplets can be fused by applying a fusion voltage tothe electrodes. The conventional techniques have a limited use due tothe following disadvantages. Firstly, relatively high voltages,sometimes in the kV range, are required for fusion of the droplets. Thisis associated with problems regarding control of the electrodes and witha disadvantageous influencing of the dispersion by the high electricfield. If, for example, sensitive macromolecules such as e.g. biologicalmacromolecules in adjacent droplets are to be made to react, themacromolecules may be damaged in the high-voltage field. Anotherdisadvantage is the limited selectivity of the droplet fusion, whichtypically involves an unspecified number of droplets in the gap betweenthe electrodes.

The objective of the invention is to provide an improved method forforming an emulsion in a fluidic microsystem, by means of which thedisadvantages of the conventional techniques are overcome and which isparticularly suitable, with a high degree of monodispersity and/or anincreased variability, for setting at least one of the parametersconsisting of droplet size, droplet composition, volume ratio of thecontinuous and dispersed phases and spatial arrangement of the dropletsof the dispersed phase. Furthermore, the method is intended to besuitable for use in a fluidic microsystem, in particular duringcontinuous operation of the microsystem (“on-line”). The objective ofthe invention is also to provide an improved fluidic microsystem forforming an emulsion, by means of which the disadvantages of theconventional techniques are overcome and which is suitable for carryingout the abovementioned method. According to further aspects, theobjective of the invention is to provide improved methods and devicesfor processing emulsions, in particular for fusing dispersed dropletsusing electric fields, by means of which the disadvantages of theconventional methods can be overcome.

These objectives are achieved by methods and devices having the featuresof the independent claims. Advantageous embodiments and uses of theinvention are defined in the dependent claims.

With regard to the method, the invention is based on the generaltechnical teaching of forming an emulsion (emulsion liquid) fromdifferent liquids which flow lined up side by side through a channel toa dispersion region, in which the width of the channel locallyincreases. The width of the channel increases in a direction differentfrom the direction in which the liquids are lined up before thedispersion region (cross-sectional widening). Upstream of the dispersionregion, a two-dimensional layer-like flow of the different liquids isformed in the channel. The channel has an elongate cross-sectionalshape, of which the smaller dimension (hereinafter: height of thechannel, channel height) is considerably smaller than the largerdimension (hereinafter: width of the channel, channel width). Thechannel height between bottom and top surfaces of the channel is sosmall that the different liquids simultaneously wet the bottom and topsurfaces as they flow through the channel. The channel width between theside surfaces of the channel is selected such that the different liquidscan pass through the channel simultaneously next to one another inpredefined volume ratios.

The liquids, which in the channel approach the dispersion region and areto be transformed into the continuous and dispersed phases in thedispersion region, form parallel flows in the channel. Each of the flowscomprises an individual, continuous liquid phase (single-phase flow).The flows are in a dynamically stable state, i.e. the interfaces betweenthe flows are oriented in a stable manner in the channel at a distancefrom the dispersion region (dynamically stable interface).

At the cross-sectional widening in the dispersion region of the channel,the channel width increases in such a way that the dynamically stablestate of the flows is destroyed. In general, this can be achieved withany cross-sectional widening which differs from the direction in whichthe flows are arranged next to one another (side by side) before thedispersion region. In practice, preference is given to a cross-sectionalwidening which extends perpendicular to the orientation of the flows, inparticular perpendicular to the channel width or parallel to the channelheight. In the dispersion region, the channel height increases to avalue at which the flows do not wet the bottom and top surfaces of thechannel in a stable manner. A transition to a dynamically unstable statetakes place in the dispersion region.

The inventors have found that, during the transition from thedynamically stable state to the dynamically unstable state, surprisinglydroplets with constant droplet diameters are formed which form thedispersed phase of the emulsion. The emulsion formed in the dispersionregion is monodisperse. While the liquid which is transformed into thedispersed phase experiences a certain Laplace pressure in the channelupstream of the dispersion region due to the interaction with the bottomand top surfaces of the channel, the Laplace pressure is reduced in thedispersion region and therefore the layer thickness of the flowincreases and a local suction effect is produced in the direction of theliquid flow. Since, as a result of this suction effect at thecross-sectional widening of the channel (dispersion region), the liquidis drawn out of the channel more rapidly than it can flow in, it ispinched off and therefore the droplet shape of the dispersed phase isformed. It has been found that this effect of reducing the Laplacepressure and forming droplets is carried out periodically with a highdegree of regularity, so that the dispersed phase is formed with a highdegree of monodispersity. The droplet size depends in particular on theextent of the cross-sectional widening in the dispersion region and canaccordingly be adjusted by modifying the channel cross section (inparticular the channel height) upstream of the dispersion region.Further possibilities for influencing the droplet size include adjustingthe viscosity and/or the flow rates of the liquids fed to the dispersionregion.

Another significant advantage of the method according to the inventionconsists in that the formation of the emulsion is brought aboutexclusively by the aforementioned transition from the dynamically stableto the dynamically unstable state, wherein this transition isindependent of the orientation of the cross-sectional widening of thechannel in the dispersion region relative to the external environment.If the microsystem is typically arranged and operated with ahorizontally oriented bottom surface, the cross-sectional widening inthe dispersion region may be obtained in particular by lowering thebottom surface, raising the top surface or a combination of lowering andraising. As an alternative, it is possible to arrange and operate themicrosystem with non-horizontally oriented bottom and top surfaces. Byway of example, the larger dimension of the channel may extendvertically and the smaller dimension of the channel may extendhorizontally before the dispersion region. In this case, thecross-sectional widening in the dispersion region is likewise orientedhorizontally.

Advantageously, there is also no particular requirement with regard tothe shape of the cross-sectional widening. The channel may widen in thedispersion region for example locally by a ramp shape of the bottomand/or top surfaces. According to a preferred embodiment of theinvention, however, a stepped cross-sectional widening is provided. Thedispersion region is formed by a step at which the channel height isincreased from a first value, at which the dynamically stable state isprovided, to a second value, at which the dynamically unstable state isprovided. One particular advantage of forming the emulsion at thestepped dispersion region consists in the improved monodispersity of theemulsion which, given a suitable choice of volumes of the continuous anddispersed phases, can be formed as a so-called crystalline emulsion.

The method according to the invention for forming emulsions cangenerally be carried out with all combinations of at least two liquidswhich have different surface tensions. In particular, direct emulsions(e.g. oil-in-water emulsions, O/W emulsions), indirect emulsions (e.g.water-in-oil emulsions, W/O emulsions) and more complex emulsions (e.g.O/W/O or W/O/W) can be formed.

If, according to another preferred embodiment of the invention, at leastone of the liquids which is to form the at least one dispersed phase inthe emulsion is fed into the channel upstream of the dispersion regionthrough at least one injection channel, further advantages are obtainedwith regard to the controllability of the emulsion formation. The atleast one injection channel opens as a side channel into one of thebottom or top surfaces of the channel. The liquid for forming thedispersed phase, which enters the channel through the injection channel,touches the bottom and top surfaces in the dynamically stable state,wherein preferably a contact angle relative to the bottom and topsurfaces is formed which is greater than or equal to 90°. In thedynamically stable state, the liquid entering the channel from theinjection channel and the liquid flowing in the channel for forming thecontinuous phase are automatically arranged in the form of the flowsdisposed next to one another. The liquid for the dispersing phase ispreferably enclosed on both sides by partial flows for forming thecontinuous phase. The partial flow on one or both sides may comprise athin film of the liquid for forming the continuous phase between thechannel wall and the phase to be dispersed.

The feeding of a plurality of flows arranged next to one another to thedispersion region in the dynamically stable state according to theinvention advantageously allows an extension such that a complexemulsion can be formed which contains for example a plurality ofdispersed phases or combined dispersed phases. For this purpose, aplurality of single-phase flows or multi-phase flows of liquids forforming the dispersed phases are arranged next to one another in amanner separated by a partial flow of the liquid for forming thecontinuous phase. The different liquids for the dispersed phases are fedvia a plurality of injection channels, which are arranged for examplenext to one another, into the channel where they run next to oneanother, in particular in parallel, to the dispersion region where thecomplex arrangements of the dispersed phases, which optionally containdifferent substances, are formed.

If, according to the invention, a plurality of different liquids fordispersed phases flow to the dispersion region, the emulsion formedtherein may advantageously contain a plurality of dispersed phases, eachof which comprises a series of dispersed droplets.

Significant advantages of the method according to the invention comparedto the conventional jet or shear techniques lie in the high degree ofconstancy of the droplet size (monodispersity) of the dispersed phaseand in the ability to set the volume ratio of the dispersed phaserelative to the continuous phase. Preferably, the droplets of thedispersed phase have droplet diameters which are less than or equal to 1mm. With particular preference, the diameters are less than 200 μm. As aresult, particularly in the case of chemical or biochemical analyses,the substance consumption can advantageously be reduced and the analysisdensity can be increased. The droplet diameters depend in particular onthe channel dimensions and on the ratio of the flow rates of the flowsbefore the dispersion region.

One important advantage of the droplet diameter in the sub-mm range,which according to the invention can be achieved with a high degree ofreproducibility, is the fact that the meta-stable state of thecomposition consisting of the continuous and dispersed phase achieved byforming the emulsion has a sufficiently long life for practical uses ofthe microsystem. The droplets of the dispersed phase can remain asdelimited compartments until the desired use, e.g. for analyticalpurposes. In order to stabilize the meta-stable state if necessary,surfactants (e.g. sorbitan mono-oleate, CAS 1338-43-8) may be added tothe liquids, e.g. to the continuous phase. However, it is not absolutelynecessary to add surfactants. By way of example, emulsions offerrofluids and water have proven to be extremely stable.

According to a further, preferred embodiment of the invention, atargeted setting of the flow rates of the single-phase flows flowing tothe dispersion region may be provided. The inventors have found that thegeometrical arrangement of the droplets of the dispersed phase in theemulsion can be reproducibly influenced as a function of the flow rateratios of the flows. In order to form the emulsion, the ratio of thevolume of the liquid for the dispersed phase flowing in per unit time tothe volume of the liquid for the continuous phase is selected in therange from 0.1 to 0.9, and for an emulsion with regularly arrangeddroplets (crystalline emulsion) is selected in the range from 0.5 to0.9. In the latter case, the droplets of the dispersed phase may formfor example two rows of droplets which are offset relative to oneanother.

If, according to a further variant of the invention, the chemicalcomposition of at least one of the liquids for the at least onedispersed phase is varied during the formation of the emulsion, theemulsion can be formed as a compartmentalized liquid comprising asuccession of droplets, the chemical composition of which varies in apredefined manner. This advantageously makes it possible to carry outscreening reactions with a high throughput rate. By way of example, theemulsion may comprise a succession of droplets having a varying pHvalue.

The invention has advantages not only for the emulsification process perse. Due to the high degree of monodispersity and the ability to controlthe geometry of the at least one dispersed phase, advantageous effectsare also achieved for further manipulation steps, in particular for afurther treatment of the emulsion. For instance, according to anadvantageous embodiment of the invention, a splitting of the emulsioninto at least two sub-emulsions may be provided. According to a firstvariant, the sub-emulsions may be formed by successions of droplets,wherein the volumes of the droplets are equal to the volume of thedroplets of the emulsion before splitting. To this end, the emulsion isformed with at least two rows of droplets which are offset relative toone another, which for splitting purposes are separated into thesub-emulsions at a branching (in particular a Y-shaped channeljunction). The separation may alternatively be for example a separationof 4 rows into 2 double rows or of 4 rows into one triple row and onesingle row or of 3 rows into one double row and one single row.

According to a second variant, the sub-emulsions may comprise dropletshaving volumes which are smaller than the volume of the droplets of theemulsion before splitting. The inventors have found that, due to thehigh degree of monodispersity and regularity of the emulsion formationwhen an individual succession of droplets meets a Y-shaped channelbranching, advantageously each droplet can be split into twosub-droplets, in particular can be halved, with an unexpectedly highdegree of regularity. The splitting of the emulsion may be provided inmultiple stages at a plurality of branchings.

According to a further embodiment which is advantageous for thetreatment and use of the emulsion formed according to the invention, acombining of sub-emulsions to form a common emulsion flow may beprovided.

The combination of the aforementioned variants of splitting andcombining emulsions and sub-emulsions may be combined as a function ofthe specific purpose of the fluidic microsystem, in order for example toproduce specific successions of droplets or successions of dropletsizes. According to a particularly advantageous variant of theinvention, the original emulsion formed may be rearranged for example.Initially the dispersed phase of the emulsion forms a straightsuccession of droplets (so-called “bamboo” structure). Afterrearrangement, the emulsion may form a plurality of parallel successionsof droplets with a smaller or identical volume which are arranged offsetrelative to one another (“zig-zag” structure).

For use of the invention, it may important to achieve interactionsbetween adjacent droplets at certain positions in the microsystem.According to a further embodiment of the invention, therefore, a fusingof two adjacent droplets of the at least one dispersed phase may beprovided. The fusion of the adjacent droplets comprises an at leastlocal break in the interface formed between the droplets by thecontinuous phase. In practice, it has proven to be particularlyadvantageous if the interface is broken by the effect of an electricfield, irradiation with light or a local increase in temperature. Theinventors have found that even a brief destabilization of the continuousphase by the electric field or the irradiation with light brings aboutfusion of the droplets.

The fusion of the droplets according to the invention may advantageouslybe provided independently of the type of droplet production. Preferably,with the method according to the invention for forming an emulsion, thedroplets are produced at a cross-sectional widening of the channel inthe microsystem. Alternatively, droplets produced using other,conventional emulsification methods can be fused according to theinvention under the effect of electric fields.

The geometric arrangement of the droplets in the emulsion can beinfluenced by adjusting the volume ratios of the liquids for thecontinuous and dispersed phase. The formation of two straightsuccessions of droplets comprising droplets arranged offset relative toone another is the result of a mutual influencing of the dropletformation in the dispersion region which was observed by the inventorsfor the first time. The droplet formation is automatically synchronizedby means of self-organization. This phenomenon can also be achieved whenforming a plurality of dispersed phases. As an alternative or inaddition to the inherent (self-organizing) droplet formation, a timecontrol of the droplet formation may be provided according to theinvention. This variant is particularly advantageous when certainanalyses, treatments or measurements on the emulsion are to besynchronized with the droplet formation. The time control may comprisefor example a synchronization of the formation of droplets of differentdispersed phases. With particular preference, the synchronization isachieved by a temporally controlled, local heating of the liquids beforethey enter the dispersion region.

With regard to the device, the abovementioned objective of the inventionis achieved by the general technical teaching of further developing afluidic microsystem for forming an emulsion, comprising a dispersionregion and a channel which leads to the dispersion region, such that thechannel upstream of the dispersion region forms a guide for atwo-dimensional flow of liquids for forming the continuous and dispersedphases of the emulsion and in the dispersion region has across-sectional widening in a direction different from thetwo-dimensional orientation of the flow in the channel before thedispersion region, in particular perpendicular to the two-dimensionalorientation.

The term “fluidic microsystem” here refers to any fluidic component withat lest two inputs for feeding in the liquids for the continuous anddispersed phases and at least one output for providing the emulsion,wherein the dispersion region is arranged preferably in the form of astep in a channel between the inputs and outputs. The fluidicmicrosystem contains channels or other cavities which in at least onedirection have a typical cross-sectional dimension in the micrometerrange (sub-mm range). The microsystem according to the invention ispreferably formed as a fluidic chip. The dispersion region is arrangedat a distance from the inputs for feeding in the liquids. The distanceis preferably at least a diameter of the droplets of the dispersedphase, preferably at least 2 mm.

In order to provide guidance for a two-dimensional flow, the channelupstream of the dispersion region has an aspect ratio (W₁/H₁) whichrepresents the quotient of the width (W₁) and height (H₁) of the channeland which is selected in the range from 100:1 to 2:1. In this range,advantageously most liquids of interest having applications inbiochemistry or analytical chemistry can form two-dimensional flows.

Advantageous variants of the microsystem according to the invention arecharacterized by at least one of the components comprising a dosingdevice for setting a flow rate of the liquids for the continuous anddispersed phases, an adjusting device for varying the chemicalcomposition of the liquid for the at least one dispersed phase, asingle-stage or multi-stage branching for splitting the emulsion, asingle-stage or multi-stage join for combining sub-emulsions, a fusiondevice for fusing adjacent compartments of dispersed phases, and asynchronization device for the time control of the droplet formation atthe dispersion region.

With regard to the method, the invention according to a further aspectis based on the general technical teaching of providing a method forprocessing an emulsion containing droplets of the dispersed phase in thecontinuous phase in a fluidic microsystem, in particular the microsystemaccording to the invention, in which at least two droplets are fusedwhen they are arranged on or move past at least two electrodes which areprovided on a wall surface of the channel of the fluidic microsystem.Preferably, the fusion takes place by subjecting the electrodes to avoltage pulse at the point in time when a first droplet is in electrical(ohmic or capacitive) contact with a first electrode and an adjacentsecond droplet is in electrical (ohmic or capacitive) contact with asecond electrode. This means that the dispersed phase of the dropletsdirectly touches the electrode surface or is separated from the latteronly by a lamella of the continuous phase which surrounds the droplets.Alternatively, an insulating layer, e.g. of a plastics material, mayadditionally be provided on the electrode material (the electrodesurface), as a result of which advantageous electrochemical side effectsare avoided.

The inventors have found that the droplet fusion does not necessarilyrequire an electrical breakthrough. Instead, a dynamic destabilizationof the lamella of the continuous phase arranged between the droplets issufficient to bring about fusion. Advantageously, there is no need touse high voltages.

According to the invention, a voltage is applied to the droplets by theelectrodes. On the droplets, an electrostatic potential is formed whichis determined or defined by the electrode voltage. The potential iseither provided by the direct electrical contact between the electrodeand the droplet, or alternatively the capacitance in each case betweenthe electrode and the droplet is comparable to or greater than thecapacitance between the droplets.

A fusion device according to the invention for fusing disperseddroplets, which fusion device forms an independent subject matter of theinvention, accordingly comprises in a channel of a fluidic microsystemat least two electrodes arranged on a wall surface of the channel and acontrol circuit for subjecting the electrodes to a voltage pulse,wherein the electrodes are arranged in such a way that, at the time offusion, the adjacent droplets to be fused are in each case in contactwith one of the electrodes.

If the voltage pulse has an amplitude of less than 15 V, particularlypreferably equal to or less than 2 V, and if the duration of the voltagepulse is less than 100 ms, particularly preferably less than 10 ms,advantages are achieved due to a particularly gentle fusion of thedispersed droplets.

A further advantage of the fusion device according to the inventionconsists in the considerable variability with regard to processingdifferently formed emulsions. If the emulsion droplets in the channel ofthe microsystem form one succession of droplets (so-called “bamboo”structure), the electrodes are preferably arranged along thelongitudinal extension of the channel. Alternatively, in order to fusedroplets which form a plurality of rows running next to one another inthe channel (“zig-zag” structure), the electrodes may be orientedtransversely to the longitudinal extension of the channel. In this case,the electrodes preferably protrude from the respective wall surface,e.g. the bottom, top or side surface of the channel, towards the centreof the channel.

Further details and advantages of the invention will become apparentfrom the following description of the appended drawings, in which:

FIG. 1 shows schematic plan and side views of a first embodiment of adevice according to the invention for forming an emulsion;

FIG. 2 shows a series of photographs of droplet production according tothe invention;

FIG. 3 shows photographs of different variants of the arrangement of thedispersed phase;

FIG. 4 shows a schematic perspective view of a further embodiment of adevice according to the invention for forming an emulsion;

FIG. 5 shows a schematic plan view of a further embodiment of a deviceaccording to the invention for forming an emulsion;

FIGS. 6 to 8 show different embodiments of synchronization devicesprovided according to the invention for the time control of dropletproduction;

FIGS. 9 to 11 show examples of embodiments of channel geometries forsplitting or combining emulsions;

FIGS. 12 and 13 show different embodiments of a positioning device usedaccording to the invention for arranging the droplets of the dispersedphase;

FIG. 14 shows further embodiments of electrode arrangements of a fusiondevice according to the invention, and

FIG. 15 shows a graph of the choice of voltage amplitudes for fusingdispersed droplets at different lamella thicknesses.

Preferred examples of embodiments of the invention will be describedbelow with reference to the features of a channel with a dispersionregion for forming an emulsion. The channel may be part of a fluidicchip or of a component for emulsion formation which is separate from afluidic chip. Details regarding such fluidic chips or other microfluidiccomponents, such as e.g. their coupling to liquid reservoirs, theproduction and control of liquid flows by pump devices, the conveying ofsamples, the flow-based influencing of the liquids and the carrying-outof measurements, are known per se from conventional fluidic microsystemtechnology and will therefore not be described in detail here.Furthermore, it is to be noted that the implementation of the inventionis not limited to the sizes, shapes and materials of the channel withthe dispersion region which are given by way of example. For instance, achannel with an elongate, rounded cross section may be provided insteadof a channel with an elongate, rectangular cross section, or a ramp maybe provided instead of a step in the dispersion region for widening thecross section.

FIG. 1 shows, in schematic views on an enlarged scale, a plan view (FIG.1A), a side view (FIG. 1B) and an enlarged sectional view (FIG. 1C) of afirst embodiment of the device 100 according to the invention forforming an emulsion. The device 100 contains a dispersion region 10which is arranged in a channel 20. The dispersion region 10 comprises astep 11, at which the channel height increases from a first value H₁ toa second value H₂. The step 11 forms the channel widening whichaccording to the invention is used to form the emulsion, and at which atransition takes place from the dynamically stable to the dynamicallyunstable state of the liquids flowing in the channel 20. A widening froma first channel width W₁ to a second channel width W₂ is optionally alsoprovided in the dispersion region 10.

The channel width W₁ is selected for example in the range from 200 μm to1000 μm. In order to form complex emulsions (see e.g. FIG. 2), a largerchannel width may be provided. The invention can also be implementedwith smaller channel widths. The height H₁ is selected in such a waythat a predefined aspect ratio W₁/H₁ is achieved, at which the liquidsflowing in the channel 20 form a dynamically stable interface.Typically, the aspect ratio should be at least 10. Accordingly, thechannel height H₁ is selected for example in the range from 5 μm to 100μm.

The channel width W₂ downstream after the dispersion region 10 isselected for example in the range from 100 μm to 1000 μm. The channelheight H₂ is for example 50 μm to 1000 μm, whereby downstream after thedispersion region the aspect ratio W₂/H₂ is considerably reduced and isfor example 0.5 to 1.

The channel 20 comprises a plane bottom surface 21, a plane top surface22 and side surfaces 23. Depending on the tool used to produce thechannel 20, the side surfaces 23 may also be plane and perpendicular tothe bottom and top surfaces 21, 22, or alternatively may be curvedrelative to at least one of the adjoining bottom and top surfaces 21,22.

An inlet opening 24 is provided in the bottom surface 21 at a distancefrom the dispersion region 10, at which inlet opening an injectionchannel 25 opens in order to inject a liquid into the channel 20. In theillustrated example (FIG. 1A), the diameter of the injection channel 25extends over the entire width W₁ of the channel 20. Alternatively, thediameter of the injection channel 25 may be smaller or larger than thechannel width W₁.

The channel 20 along with the dispersion region 10 and the injectionchannel 25 are provided for example in a chip body of a fluidicmicrosystem. The chip body is produced in one or more parts andpreferably has at least one part (e.g. a cover plate) made from atransparent material, e.g. plastic. As the material for the chip body,use is made for example of PMMA, which is advantageously opticallytransparent and is inert for most liquids of interest. As analternative, the chip body or parts thereof may be made from othermaterials, such as e.g. glass or silicon.

According to an advantageous embodiment of the invention, the chip bodyhas an electrically conductive layer on at least one surface facingtowards the interior of the channel or branch (see below).Advantageously, the conductive layer may be placed at a predefinedpotential or a free potential (“floating”) in order to avoid undesirablecharging of the emulsion. The potential is selected in such a way thatit equalizes an electrostatic potential of the droplets in the emulsion.The conductive layer may be provided for example on the bottom and/ortop surfaces and may be for example at ground potential or at a freepotential. This embodiment of the invention is particularly advantageousfor emulsions which have a foam-like structure (small volume of thecontinuous phase), since these have proven to be extremely sensitive toelectrostatic charges.

In order to form the emulsion 1 with a continuous phase 2 and adispersed phase 3, flows 4, 5 of the different liquids for thecontinuous and dispersed phase are provided in the channel 20. The flows4, 5 contain the corresponding liquids in each case as an individualliquid phase. In the illustrated example, two flows 4, 5 are produced.The flow 4 comprising the liquid for the dispersed phase 3 is enclosedon both sides by the flow 5 comprising the liquid for the continuousphase 2. FIG. 1C schematically shows, in an enlarged sectional view, thedynamically stable interface between the flows 4 and 5. The flow 4 ofthe liquid for the dispersed phase extends between the bottom and topsurfaces 21, 22 of the channel 20. The bottom and top surfaces 21, 22are directly touched by the flow 4, or else they are separated from theflow 4 by a (mesoscopic or molecularly thin) film of the liquid for thecontinuous phase.

The continuous phase comprises for example an organic solvent based onhydrocarbons (e.g. Isopar M, product name), while the dispersed phasecomprises aqueous solutions or dispersions. The flow rate in the channelis e.g. around 10 to 100 mm/s.

As a result of the destabilization of the flows 4, 5 at the step 11, thedispersed phase 3 of the emulsion 1 which is distributed in thecontinuous phase 2 is formed. Unlike the conventional techniques, theformation of the droplets 6 of the dispersed phase 3 is based not on theeffect of shear forces or a Rayleigh instability, but rather on thedestruction of the dynamic stability before the step 11 and theformation of a new state of equilibrium under the effect of the surfacetension and the Laplace pressure, which is reduced at the step 11.Advantageously, the cross-sectional widening of the channel 20 which isprovided by the step 11 represents a considerably simplified channelgeometry. Furthermore, an excellent monodispersity of better than 1.5%can be achieved in the emulsion. The droplet volumes can be setessentially by the channel height H₁ and the channel width W₁, while theflow rate has barely any influence on the droplet size.

Another advantage of the emulsion formation at the step 11 is that noadditional droplets (so-called satellite droplets) are formed. Thepinching-off at the step 11 takes place at a high speed (pinching-offwithin a few milliseconds), so that a reliable pinching-off of eachdroplet is possible.

FIGS. 2A to 2F are photographs of the process of pinching-off a droplet6 of the dispersed phase 3, said photographs in each case being recordedat a time interval of 2 ms. FIG. 2A shows, upstream of the step 11, theflows 4 and 5 for the dispersed and continuous phase. A channel wideningaccording to FIG. 1 is provided at the step 11. Downstream after thestep 11, the channel is filled with the emulsion 1 comprising thecontinuous phase 2 and the dispersed phase 3. FIG. 2A shows thesituation when the pinching-off of a droplet at the step 11 has justfinished. Shortly thereafter, further liquid of the flow 4 passes overthe step 11 (FIGS. 2B, 2C). After passing the step 11 and after thereduction in the Laplace pressure acting on the flows 4, 5, the nextdroplet grows (FIGS. 2D, E), which draws liquid out of the flow 4upstream of the step 11 as a result of the reduced Laplace pressure. Asa result, during the pinching-off process (FIG. 2F), a gap 7 can be seenbetween the droplet that has just been pinched off and the flow 4. Aftera widening of the end of the flow 4 (see FIGS. 2A, B), the gap 7 is thenbreached by the subsequent flowing liquid, so that the next droplet canbe formed.

The volume of the droplets 6 of the dispersed phase 3 depends on theratio of the flow rates of the flows 4, 5. For the quotient of the flowrates of the flow 4 (for the dispersed phase) and the flow 5 (for thecontinuous phase) in the range from 0.1 to 0.8, an essentially lineardependency of the droplet volume is obtained in the range from 0.1 nl to0.4 nl (total flow rate: 147 μl/h, channel height H₁: 10 μm). Thefrequency of droplet production can also be set as a function of theflow rate. For flow rates of the flow 4 (for the dispersed phase) of upto 0.15 μl/s, linear dependencies of the frequency of droplet productionwere found which for larger droplet volumes (e.g. 2.6 nl) were up to 50Hz and for smaller droplet volumes (e.g. 0.3 nl) were up to 120 Hz. Theupper limit of the frequency of droplet formation depends on theinterface tension, the viscosities of the dispersed and continuousphase, and the droplet volume. The high droplet frequencies achievedaccording to the invention while simultaneously providing good controlof the droplet volume and monodispersity are an important advantage ofthe invention for industrial applications in the case of “on-line”emulsification in the fluidic microsystem or a corresponding component.

The flow rates are controlled by a dosing unit (not shown), whichcomprises e.g. a dosing pump or an injection pump.

FIGS. 3A to 3C illustrate how the geometric arrangement of the dispersedphase in the emulsion can be influenced by adjusting the ratios of theflow rates. In the case of a volume of the liquid for the dispersedphase of 55% (FIG. 3A), the droplets of the dispersed phase form anunordered packing. For a larger volume of e.g. 79% (FIG. 3B) or 85%(FIG. 3C), an ordered, foam-like arrangement is obtained, in which thevolume of the emulsion is substantially formed by the volume of thedroplets of the dispersed phase, which are separated from one another bythin layers of the continuous phase. Using the technique according tothe invention, the formation and manipulation of foam-like, regularstructures in liquid/liquid systems is possible for the first time,which were previously achieved only in liquid/gas systems with largerdimensions. An arrangement of the droplets according to FIG. 3C can alsobe achieved by simultaneously producing two dispersed phases (seebelow).

FIG. 4 shows part of a modified embodiment of the device according tothe invention in a schematic perspective view showing the dispersionregion 10, the channel 20 and the injection channel 25. The structureand function of the embodiment of the invention shown in FIG. 4corresponds substantially to the details already discussed withreference to FIG. 1, but the channel 20 and the step 11 of thedispersion region 10 are oriented differently in space compared toFIG. 1. The elongate cross-sectional shape of the channel 20 extends inthe z-direction, i.e. in the vertical direction, while the step 11 formsa cross-sectional widening in the horizontal direction. It is asignificant advantage of the invention that the formation of theemulsion is essentially independent of the effect of gravity and thusindependent of the orientation of the device 100 in space. In the systemaccording to FIG. 4, too, the droplets of the dispersed phase (notshown) can be pinched off after the destabilization of the flows at thestep 11.

If an emulsion containing a plurality of different dispersed phases isto be formed using the device 100 according to the invention, it isadvantageously possible to use a structure which is shown in a schematicplan view in FIG. 5. The device 100 again contains the dispersion region10 with the step 11 in the channel 20. Three injection channels 25.1,25.2 and 25.3 open into the bottom surface 21 of the channel 20, throughwhich identical or different liquids can be injected into the channel 20in order to form a plurality of dispersed phases. The flows 4.1, 4.2 and4.3 are embedded in the flow 5 of the liquid for the continuous phase asdescribed above. By simultaneously pinching off the droplets at the step11, three dispersed phases are formed which, when a high volume of theflows 4.1, 4.2 and 4.3 compared to the flow 5 is set, are separated fromone another only by thin lamellae of the continuous phase. The structureshown in FIG. 5, which can be extended in an analogous manner to four ormore injection channels, thus allows the targeted arrangement ofdifferent substances in adjacent droplets (compartments) of thedispersed phase in the emulsion 1. The emulsion droplets produced by thearrangement shown in FIG. 5 can in each case have different volumesdepending on the flow volumes of the flows 4.1, 4.2 and 4.2 that areset.

When forming an emulsion containing a plurality of dispersed phases asshown in FIG. 5, the droplets of the dispersed phases may form a regulargeometric arrangement as a result of self-organization, e.g. analogouslyto FIG. 3C with three straight successions of droplets which arearranged offset relative to one another. This self-alignment is achievedin particular in the case of high volume ratios, that is to say whenthere is a large volume of the dispersed phase in the emulsion. Themutual alignment of the droplets, particularly also in the case of lowvolume ratios, can be improved by a time control of the pinching-off ofthe droplets, which will be described below with reference to FIGS. 6 to8.

FIG. 6 shows an embodiment of the device 100 according to the inventionwhich is analogous to FIG. 5, wherein a synchronization device 30 isadditionally provided for the time control of the droplet formation. Theschematically shown synchronization device 30 comprises a heating strip31 which is arranged running along the bottom surface 21 perpendicularto the flow direction in the channel 20. The heating strip 31 isdesigned e.g. for resistance heating and consists of a thin strip ofmetal or another electrically conductive material. The width of theheating strip 31 is e.g. 2 to 100 μm.

The heating strip 31 is connected to a control circuit (not shown), bymeans of which the heating strip 31 is subjected to electric currentpulses. As a result of the current pulses, a local heating of theliquids in the channel 20 is achieved. As a result of the local heating,a so-called Marangoni transport is produced in the liquids (convectionbased on the Marangoni effect), which brings about synchronization ofthe pinching-off of droplets at the step 11. As a result of theMarangoni effect, the interface tension between the different liquids(e.g. between the oil and water phases) is spatially and temporallymodulated. The constant flow from the injection channels 25.1, 25.2 and25.3 to the step 11 is thus superposed with an oscillatory flow whichinfluences the pinching-off of droplets. The inventors have found thatthe frequency of the pinching-off of droplets corresponds to thefrequency of the current pulses on the heating strip 31. Since theMarangoni effect is very pronounced in the fluidic microsystem,advantageously low heating currents which provide heating by a fewdegrees are sufficient to achieve the described synchronization.

If the droplets are to be produced simultaneously at the step 11, theheating strip 31 for all the flow regions is arranged at the samedistance from the step 11. If the droplet production is to follow aspecific time schedule, a synchronization device with a modified heatingstrip 32 may be provided as shown in FIG. 7. The heating strip 32 has acurved profile, so that the local heating for the outer flows 4.1 and4.3 takes place at a smaller distance y₁ from the step 11 than for thecentral flow 4.2, for which the local heating takes place at a greaterdistance y₂ from the step 11. The distances y₁ and y₂ are e.g. 100 μmand 200 μm. As a result, the droplets from the flows 4.1 and 4.3 areproduced in a manner that is temporally offset relative to the dropletsof the flow 4.2. The droplets of the dispersed phase are offset relativeto one another and form a so-called honeycomb structure.

The time control of the emulsion formation by the synchronization device30 may be advantageous not only in the case of the embodiment shown inFIG. 5 but also in the event of parallel operation of a plurality ofdevices 100, 101, 102 for forming emulsions, as illustratedschematically in FIG. 8. The droplets of the dispersed phase are formedin the channels 20 according to a predetermined time schedule, which isdefined by the pulsed application of heating currents to the heatingstrip 31 running across all three channels. The heating strips may beformed separately for each channel and may be actuated separately. Atriggering of the pinching-off processes relative to one another whichis variable and can be controlled in a targeted manner is thus possible.The channels 20 may subsequently be combined to form a common channel(see below) in which the dispersed phases have a predefined geometricorientation relative to one another.

The synchronization of the droplet production is particularlyadvantageous in applications of the invention where the relativeposition of the droplets (compartments) of the dispersed phase is to becontrolled. If, for example, an emulsion containing two dispersed phasesas shown in FIG. 3C is produced using two parallel injection channels(analogously to FIG. 5), the composition, e.g. the pH value, of one ofthe two dispersed phases can be continuously varied. The pH value mayincrease in steps from droplet to droplet over e.g. 100 droplets frompH=3 to pH=11. In order to be able to monitor in a reproducible mannerthe result of the reaction of the contents of droplets having such aprecisely defined composition, it must also be possible to set theposition of the individual droplets in a reproducible manner as the flowcontinues.

The chemical composition of the liquid for the dispersed phase iscontrolled by an adjusting device (not shown), which comprises e.g. acombination of dosing pumps or injection pumps.

According to the invention, a rearrangement of the successions ofdroplets may be provided in order to bring droplets having predefinedcompositions into the direct vicinity of one another for a chemicalreaction. The rearrangement may be achieved by means of channelstructures which will be described below by way of example withreference to FIGS. 9 to 13.

According to FIG. 9, the channel 20 of the device 100 according to theinvention is connected to a splitter device 40 which comprises aplurality of channel branchings 41, 42 and 43. A joining device 50 isalso provided, at which the branches of the channel 20 are combinedagain at joins 51, 52 and 53. The rearrangement or manipulation of anemulsion in the channel 20 takes place as a function of the dropletarrangement before entering the splitter device 40 and the length of thebranches between the channel branchings 41, 42 and 43 and the joins 51,52 and 53.

If the emulsion comprises two straight successions of droplets arrangedoffset relative to one another (analogously to FIG. 3C) before enteringthe splitter device 40, the two successions of droplets are separatedfrom one another at the first branching 41. One single succession ofdroplets arranged one behind the other (“bamboo” structure) is thenlocated in each of the branches 44, 45, said droplets being split at thebranchings 42 and 43 into partial droplets with half the volume. Thishalving is illustrated in the photograph shown in FIG. 10.Advantageously, according to a modified variant, the volume of thedroplet can be split unequally into two droplets depending on the flowrates in the individual channels of the Y-junction. In the joiningdevice 50, the sub-emulsions in the individual branches are combinedagain, with two straight successions of droplets arranged offsetrelative to one another being formed as a result. With regard to whichdroplets are adjacent to one another, this depends on the length of thebranches 44, 45, 46, 47, 54 and 55.

If an emulsion with the “bamboo” structure is already provided beforeentering the splitter device 40, the droplets thereof are halved at thefirst branching 41, so that after passing through the joining device 50an emulsion having the “zig-zag” structure is formed, in which thevolumes of the partial droplets are quartered compared to the dropletsbefore the splitter device.

An interaction between adjacent droplets 6, 8 of an emulsion formedaccording to the invention can be achieved by breaking through theseparating layer of the continuous phase arranged between the droplets.To this end, use may be made of a fusion device 60, which is illustratedby way of example in FIGS. 9 and 14. The fusion device 60 comprises twoelectrodes 61, 62 which are arranged for example on the bottom surfaceof the channel 20 and are connected to a control circuit 80 (not shownin FIG. 14). As two droplets 6, 8 which are to be made to interact passacross the electrodes 61, 62, said electrodes are subjected to a briefvoltage pulse. Under the effect of the electrical voltage, theseparating layer between the droplets 6, 8 is broken through, whichleads to the fusing of said droplets. The interaction comprises forexample a chemical reaction between the substances contained in thedroplets or a reaction of biological materials which are contained inthe droplets in suspended form. The voltage pulse applied in order tofuse two adjacent droplets has e.g. an amplitude of 2 V and a durationof 10 ms or 100 ms.

According to FIG. 14A, the electrodes 61, 62 are formed by electricallyconductive layers which are arranged one behind the other in thelongitudinal direction of the channel (see arrow), with a slight gapbeing provided between the electrodes. The gap between the electrodes issmaller than the axial length of the droplets 6, 8 in the longitudinaldirection of the channel. The upper part of FIG. 14A shows how thedroplets 6, 8 to be fused move past the electrodes 61, 62. When thelamella between the droplets 6, 8 is arranged over the gap, i.e. when ineach case one of the droplets 6, 8 is in contact with one of theelectrodes 61, 62, a voltage pulse is applied to the electrodes 61, 62.As a result, the fused droplet 9 forms as shown in the lower part ofFIG. 14A.

FIG. 14B shows a corresponding electrode arrangement for fusing dropletswhich form adjacent rows of droplets (“zig-zag” structure) in thechannel 20. When the droplets 6, 8 to be fused move past the electrodes61, 62 on a top surface of the channel 20, a voltage pulse is applied tosaid electrodes so that the fused droplet 9 is formed. The electrodes61, 62 are formed by electrically conductive layers which, in thelongitudinal extension of the channel 20, have a width that is smallerthan the droplet width. As an alternative, wire-type electrodes 61, 62may be arranged in the channel 20, for example on one or more of thewalls thereof.

The right time to apply the voltage pulse to the electrodes can bedetermined by a sensor device (not shown), by means of which therespective position of the droplets 6, 8 in the channel 20 of themicrosystem is detected. The sensor device may be based for example onan electrical or optical detection of the droplet position.

FIG. 15 shows experimental results obtained with the fusion deviceaccording to the invention. The amplitude (U) of the voltage pulse forfusing the droplets is shown as a function of the distance between thedroplets, i.e. the thickness of the lamella of the continuous phaseprovided between the droplets, for different dispersed phases. As thedistance between the dispersed droplets increases, an increasing voltageamplitude is required for the electrocoalescence of the droplets,although advantageously voltages below 12 V are sufficient forelectrocoalescence in the range of interest below a distance of 10 μm.If, according to the abovementioned embodiment of the invention, anelectrically conductive layer is provided on the bottom and/or topsurfaces, this layer is interrupted in the vicinity of the electrodes ofthe fusion device.

The fusion device 60 may be modified such that, instead of the twoelectrodes 61, 62 that are shown, one or more electrode arrays whicheach comprise a plurality of electrodes are provided. The electrodes maybe arranged on at least one of the bottom, top and side surfaces of thechannel 20. The actuation of the electrodes may be selected as afunction of the droplet size produced in the specific application.

A modified variant of a joining device 50.1 for combining a plurality ofemulsions in multiple stages is shown in a schematic plan view in FIG.11. The individual emulsions flow together e.g. via the branches 54, 55and joining points 53 (see arrow direction), until an essentiallytwo-dimensional arrangement of the dispersed phases is achieved in thechannel 20. By way of example, 16 rows of droplets arranged offsetrelative to one another may run in parallel in the channel 20. Thiscombining of the emulsions may be advantageous for example forbiochemical uses of the invention. The emulsion in the channel 20 formsa droplet array which can be read like a substance library e.g. byoptical means.

In a further modified variant of a joining device for combining aplurality of emulsions in multiple stages, a three-dimensionalarrangement of the droplets may be formed. In this case, the branchescontaining individual rows of droplets or containing a two-dimensionalarrangement of droplets, e.g. as shown in FIG. 11, fuse at the joiningpoints relative to one another with a vertical orientation.

The transformation of an emulsion comprising a straight succession ofdroplets arranged one behind the other (“bamboo” structure) into anemulsion comprising two rows of droplets arranged offset relative to oneanother (“zig-zag” structure) is shown schematically in FIGS. 12 and 13.A positioning device 70 which is used according to the invention isformed by a second channel widening, at which the channel widthincreases to a third value W₃. The channel width W₃ corresponds e.g. totwice the channel width W₂ before the second channel widening. Thedroplets moving through the channel 20 from the left in FIG. 12, afterpassing the positioning device 70, form a pattern of droplets arrangedoffset relative to one another in the flow direction (“zig-zag”structure). As shown in FIG. 13, the positioning device 70 mayadditionally have a branching 71, at which the partial successions ofrearranged droplets are separated into different branches 72, 73.

The features of the invention which are disclosed in the abovedescription, the drawings and the claims may be important bothindividually and in combination with one another for implementing theinvention in its various embodiments.

1. A method for forming an emulsion including at least one dispersedphase and a continuous phase in a fluidic microsystem, said methodcomprising the following steps: forming flows of different liquids whichflow towards a dispersion region, and forming the emulsion from theliquids in the dispersion region, wherein the flows run through a commonchannel to the dispersion region, wherein the flows are arranged next toone another relative to a first reference direction, and the emulsion isproduced as the liquids flow through a cross-sectional widening providedin the dispersion region, at which the cross section of the channelwidens in a second reference direction different from the firstreference direction.
 2. The method according to claim 1, in which theemulsion is produced as the liquids flow over a step provided in thedispersion region.
 3. The method according to claim 2, in which at leastone of the flows is fed into the channel through at least one injectionchannel.
 4. The method according to claim 3, in which a plurality offlows is fed into the channel at a plurality of injection channels. 5.The method according to claim 1, in which the at least one dispersedphase comprises droplets, the diameter of which is less than 1000 μm. 6.The method according to claim 5, in which the at least one dispersedphase comprises droplets, the diameter of which is less than 200 μm. 7.The method according to claim 1, further comprising the following step:setting a predefined flow rate ratio which is a quotient of a flow rateof the flow for the dispersed phase and of a flow rate of the flow forthe continuous phase.
 8. The method according to claim 7, in which theflow rate ratio is set in the range from 0.1 to 0.9.
 9. The methodaccording to claim 8, in which the flow rate ratio is set in the rangefrom 0.5 to 0.9.
 10. The method according to claim 1, further comprisingthe following step: varying a chemical composition of at least one ofthe liquids.
 11. The method according to claim 10, in which the at leastone dispersed phase is formed as a succession of droplets, a chemicalcomposition of which varies.
 12. The method according to claim 10, inwhich the at least one dispersed phase is formed as a succession ofdroplets, each of which has a different pH value.
 13. The methodaccording to claim 1, in which the emulsion contains a plurality ofdispersed phases, each of which comprises a succession of disperseddroplets.
 14. The method according to claim 1, further comprising thefollowing step: splitting the emulsion into at least two sub-emulsions.15. The method according to claim 14, in which the sub-emulsions aftersplitting comprise droplets having a volume that is equal to a volume ofthe droplets of the emulsion.
 16. The method according to claim 14, inwhich the sub-emulsions after splitting comprise droplets having avolume that is smaller than a volume of the droplets of the emulsion.17. The method according to claim 14, in which the splitting of theemulsions takes place in multiple stages at a plurality of branchings.18. The method according to claim 14, further comprising the followingstep: combining the sub-emulsions to form a common emulsion flow. 19.The method according to claim 1, comprising the step: rearranging theemulsion from a state in which the dispersed phase forms a simplesuccession of droplets to a state in which the dispersed phase forms aplurality of successions of droplets which are offset relative to oneanother.
 20. The method according to claim 1, further comprising thefollowing step: fusing two adjacent droplets of the at least onedispersed phase.
 21. The method according to claim 20, in which thefusion takes place under the effect of an electric field, irradiationwith light or local heating.
 22. The method according to claim 1,further comprising the following step: synchronizing the formation ofdroplets of the at least one dispersed phase as a function of at leastone time schedule.
 23. The method according to claim 22, in which thesynchronizing comprises a time control of the formation of droplets of aplurality of dispersed phases relative to one another.
 24. The methodaccording to claim 22, in which the synchronizing comprises a temporallycontrolled heating of the flows upstream of the dispersion region.
 25. Afluidic microsystem for forming an emulsion including a continuous phaseand at least one dispersed phase, said fluidic microsystem comprising: adispersion region for forming the emulsion from different liquids, and achannel which leads to the dispersion region, wherein the channel isdesigned in such a way that flows of the liquids in the channel run nextto one another relative to a first reference direction, and the channelhas in the dispersion region a cross-sectional widening at which a crosssection of the channel widens in a second reference direction differentfrom the first reference direction.
 26. The microsystem according toclaim 25, in which the cross-sectional widening comprises a step. 27.The microsystem according to claim 25, in which the channel has anaspect ratio (W₁/H₁), calculated from a width (W₁) parallel to the firstreference direction and a height (H₁) perpendicular to the firstreference direction, which is selected in a range from 100:1 to 2:1. 28.The microsystem according to claim 25, in which at least one injectionchannel is connected to the channel, through which injection channel atleast one of the flows can be fed into the channel.
 29. The microsystemaccording to claim 28, in which the channel is connected to a pluralityof injection channels, at which a plurality of flows can be fed into thechannel.
 30. The microsystem according to claim 25, which has a dosingdevice for setting a predefined flow rate ratio of the flows.
 31. Themicrosystem according to claim 25, which has an adjusting device forvarying a chemical composition of at least one of the liquids.
 32. Themicrosystem according to claim 25, which has a splitter device with atleast one branching for splitting the emulsion into at least twosub-emulsions.
 33. The microsystem according to claim 32, in which thesplitter device has a plurality of branchings for splitting the emulsionin multiple stages.
 34. The microsystem according to claim 32, which hasa joining devices for combining the sub-emulsions to form a commonemulsion flow.
 35. The microsystem according to claim 25, which has atleast one fusion device for fusing two adjacent droplets of the at leastone dispersed phase.
 36. The microsystem according to claim 35, in whichthe fusion device comprises electrodes for generating an electric field,a light source or a heating device.
 37. The microsystem according toclaim 25, which has at least one synchronization device forsynchronizing a formation of droplets of the at least one dispersedphase as a function of at least one time schedule.
 38. The microsystemaccording to claim 37, in which the synchronization device has a heatingdevice which is arranged in the channel.
 39. A method for processing anemulsion containing droplets of a dispersed phase in a continuous phasein a fluidic microsystem according to claim 25, said method comprisingthe following steps: passing two droplets, which are to be made tointeract, across electrodes which are arranged on at least one wallsurface of a channel of the fluidic microsystem, subjecting theelectrodes to a voltage pulse, and fusing the droplets.
 40. The methodaccording to claim 39, in which the electrodes are subjected to thevoltage pulse when in each case one of the droplets is in contact withone of the electrodes.
 41. The method according to claim 39, furthercomprising the following step: selecting parameters for controlling theelectrodes as a function of a size of the droplets.
 42. The methodaccording to claim 39, in which the electrodes are subjected to avoltage pulse having an amplitude of less than 15V.
 43. The methodaccording to claim 39, in which the electrodes are subjected to avoltage pulse having a duration of less than 100 ms.
 44. A fusion devicefor fusing droplets of a dispersed phase in a continuous phase in achannel of a fluidic microsystem according to claim 25, said fusiondevice comprising: at least two electrodes which are arranged on atleast one wall surface of a channel of the fluidic microsystem, and acontrol circuit which is designed to subject the electrodes to a voltagepulse when the droplets move past the electrodes.
 45. The fusion deviceaccording to claim 44, in which the control circuit is designed tosubject the electrodes to a voltage pulse having an amplitude of lessthan 15 V.
 46. The fusion device according to claim 44, in which thecontrol circuit is designed to subject the electrodes to a voltage pulsehaving a duration of less than 100 ms.
 47. The fusion device accordingto claim 44, in which the electrodes are arranged in such a way that anelectric field can be produced with a direction differing from alongitudinal extension of the channel.
 48. The fusion device accordingto claim 47, in which the electrodes are arranged in such a way that anelectric field can be produced with a direction oriented transversely tothe longitudinal extension of the channel.
 49. The fusion deviceaccording to claim 47, in which the electrodes are arranged on the atleast one wall surface of the channel in such a way that they protrudefrom two sides towards a center of the channel.
 50. The fusion deviceaccording to claim 44, in which the electrodes are arranged in such away that an electric field can be produced with a direction which runsparallel to a longitudinal extension of the channel.
 51. The fusiondevice according to claim 44, in which the electrodes compriseelectrically conductive layers on the at least one wall surface of thechannel.
 52. The fusion device according to claim 44, in which the atleast two electrodes comprise one or more electrode arrays in each casewith a plurality of electrodes which are arranged on at least one of abottom, top and side surfaces of the channel.